The Management of Solitary Trichoepithel Ioma Versus Basal Cell

The management of M. VOTRUBA, C.M.P. COLLINS, R.A. HARRAD solitary trichoepithel ioma versus basal cell carcinoma

Abstract Trichoepithelioma is a benign tumour of the hair follicleS and is one of a group of follicular Currently, all lesions diagnosed clinically as basal cell carcinoma (BCC) are treated by the tumours. It may be solitary or multiple.6 excision of the lesion with 3--4 mm margins Multiple trichoepithelioma is inherited in an followed by histopathological examination to autosomal dominant pattern? The first lesion assess clearance and confirm the diagnosis. often appears in childhood and there are We present the findings of surgical incisional numerous rounded, skin-coloured firm papules and excisional biopsy of three young patients measuring 2-8 mm diameter, especially in the diagnosed on clinical examination as having nasolabial folds, nose, forehead and upper lip. BCC, who were found on histological Solitary trichoepithelioma is more common than examination to have trichoepithelioma. Whilst it may be possible to distinguish the features multiple and it is not inherited. It is a firm, of trichoepithelioma in incisional biopsy elevated flesh-coloured nodule less than 2 em in specimens on morphological grounds alone it diameter and rarely ulcerates. It appears in is often difficult, and immunohistochemical early adult life,8 most commonly on the face. staining, to delineate the features of the The histopathology of solitary basement membrane, provides useful trichoepithelioma shows a high degree of additional information in the histological differentiation towards hair structures and diagnosis. As trichoepithelioma is more contains numerous horn cysts and abortive common in the young it should be considered primitive hair papillae9 (Fig. 1) as well as in the differential diagnosis in young patients presenting with BCC-like lesions of the narrow strands of tumour cells. There is a low periocular tissues. This subgroup of patients mitotic rate and a desmoplastic stroma, with a should have incisional biopsy carried out, and low quantity of stromal mucin.10 if the diagnosis of trichoepithelioma is BCC is the most common skin cancer among confirmed the lesion may be excised with a whites, accounting for 80% of the 600 000 new small margin of healthy tissue, thereby cases of non-melanoma skin cancer in the USA facilitating surgical repair. each year.ll It is also the most common skin cancer of the lid, accounting for 80-90% of Key words Eyelid, Eyelid tumours, cases.12 Classically, it occurs in the sun-exposed Trichoepithelioma, Basal cell carcinoma, areas, especially of fair-skinned elderly people. Reconstructive surgery Ninety-five per cent of all BCCs occur in people between 40 and 79 years old, with the average age for BCC of the lid being nearly 60 years; peak incidence occurs in the seventh and eighth The distinction between basal cell carcinoma decades. (BCC) and trichoepithelioma is of clinical BCC is a slow-growing, shiny, skin-coloured, M. Vortruba, importance, since conventionally a BCC should RA Harrad � translucent, raised papule, with telangiectasia Bristol Eye Hospital be excised with a 3-4 mrn margin of healthy on the surface and central ulceration. It has a Lower Maudlin Street tissue,l whilst trichoepithelioma may only rolled border and a crusted centre. It is locally Bristol BS1 2LX, UK require shave biopsy or minimal resection.2 The Tel: +44 (0)117 928 4689 invasive and rarely, if ever, metastasises. Two recurrence rate for trichoepithelioma treated by Fax: +44 (0)117 928 4686 shave biopsy or minimal resection is low, as is main forms are seen: the rodent ulcer (typically C.M.P. Collins the recurrence rate for trichoepithelioma treated as described above) and the flat, cicatrising Department of Pathology morpheaform or sclerosing BCe, whose by the non-surgical techniques of argon laser3 or Bristol Royal Infirmary cryotherapy.4 margins are clinically difficult to delineate. Bristol, UK

Eye (1998) 12,43-46 © 1998 Royal College of Ophthalmologists 43 is also expression of these proteins as globular deposits within the mass of the tumour,16 reflecting, it is thought, the disordered maturation of the cells in BCe. We have stained our cases of trichoepithelioma and parallel cases of BCC for collagen IV and laminin to demonstrate that differences in expression of the basement membrane proteins in these two tumours may be of help in distinguishing them in small incisional biopsies. Recent reports1B,19 have also suggested that staining for bC/-2 and CD34 is useful in differentiating BCC and trichoepithelioma. CD34 is an antigen that stains the spindle-shaped cells in the middle portion of the normal hair follicle. bC/-2 is a proto-oncogene associated with

Fig. 1. Trichoepithelioma with horn cysts (H&E, low power). programmed cell death. These two stains were also used in our cases. We report three cases of young adults diagnosed on Histological examination shows masses of compactly clinical examination as having atypical BCC who, on arranged basaloid cells, resembling cells in the basal histological examination, were found to have layer of epidermis, with a variable stromal reaction. trichoepithelioma. There is characteristic palisading of dark epithelial cells 13 (Fig. 2). It can be difficult to distinguish BCC and Case reports trichoepithelioma on purely morphological grounds on a Case 1 small incisional biopsy. Immunohistochemical staining A 32-year-old woman presented with a 2 year history of techniques show more clear differences between BCC an elevated, pearly and nodular lump on her right cheek and trichoepithelioma. measuring 4.5 X 5.5 mm (Fig. 3). It was diagnosed It is thought that BCC spreads by local invasion clinically as a BCe. The patient had an excisional biopsy because it produces a basement membrane - a feature with 3 mm margins and direct closure of the defect. that is largely lost in tumours that exhibit widespread Histopathological examination showed complete dissemination. The nature of the basement membrane in excision of a trichoepithelioma (Fig. 4). BCC has been examined by both electron microscopy'4,15

and immunohistochemical techniques, and the presence Case 2 of normal basement membrane components including A 43-year-old man presented with a 1 year history of a laminin, bullous pemphigoid antigen, collagen IV and lesion on the right medial canthus (Fig. 5). It was plaque collagen V has been established.16,17 Two points arise like and pearly. A clinical diagnosis of a BCC was made from the investigation of basement membrane in BCe. and an incisional biopsy was performed. Firstly, on ultrastructural examination the basement Histopathological examination of the small segment membrane surrounding a BCC is seen to be suggested a BCC with trichoepitheliomatous discontinuousl4,15 and, secondly, while in normal differentiation. An excisional biopsy was performed with epithelial basement membrane proteins are expressed a clear 4 mm margin. Further histology showed a only at the basal pole of the epithelial layer, in BCC there trichoepithelioma (Fig. 6). A right glabellar flap reconstruction was performed.

Case 3

A 32-year-old woman presented with a 1 year history of a left lower lid lump. She was seen in the Accident and Emergency Department where an incision and curettage was performed. The lump was noted to be composed of fibrosed tissue and she was referred for incisional biopsy. The lesion was 15 mm in diameter, oval, raised, with no central umbo or ulceration (Fig. 7). The central nests of cells were atypical of BCC, suggesting a trichoepithelioma (Fig. 8). Nevertheless, excision with 3 mm margins was performed. Histopathological examination distinguished the lesion from a sclerosing

Fig. 2. Basal cell carcinoma showing clear palisading of dark epithelial BCC and confirmed a trichoepithelioma. A Hughes cells (H&E, low power). repair was carried out.

44 Fig. 4. Case 1. Complete excision of trichoepithelioma showing characteristic horn cysts, primitive hair follicles, low mitotic rate and low quantity of stromal mucin (H&E, low power).

Fig. 3. Case 1.

Fig. 6. Case 2. Trichoepithelioma showing keratin formation (H&E, high power). Fig. 5. Case 2.

Fig. 8. Case 3. Histology showing central nets of cells with keratin Fig. 7. Case 3. horn cysts (H&E, high power).

45 Results Conclusion

In our cases of trichoepithelioma we found the Current practice is to treat all lesions clinically diagnosed expression of a continuous layer of basement membrane, as BCC in the same way, with excision of the lesion with as defined by staining for collagen IV and laminin at the 3-4 mm margins of healthy tissue. We feel that the periphery of the tumour lobules, which was essentially diagnosis of trichoepithelioma should be suspected in indistinguishable from that of normal epithelia. There young patients, and incisional biopsy carried out to was no evidence of expression of these proteins within confirm the diagnosis, in order to conserve tissue and the tumour mass. avoid excessively mutilating surgery. In contrast, the expression of collagen IV and laminin in the basement membrane zone of BCC was patchy, We thank Mrs G. Bennerson for preparation of the illustrations. discontinuous and ill-defined, and there was evidence of deposition of this protein within the tumour mass. References Although the distribution of staining for laminin and 1. Wolf DJ, Zitelli JA. Surgical margins for basal cell carcinoma. collagen IV was similar, laminin stained more weakly Arch Dermatol 1987;123:340-4. 2. Simpson W, Garner A, Collin JR. Benign hair-follicle derived and was harder to interpret. tumours in the differential diagnosis of basal cell carcinoma CD34 was strongly positive in our cases of of the eye-lids: a clinicopathological comparison. Br J trichoepithelioma but positive only for the blood vessels Ophthalmol 1989;73:347-53. 3. Flores JT, Apfelberg DB, Maser MR, Lash H. in the BCe. Trichoepithelioma: successful treatment with argon laser. Only the outer cells of the trichoepithelioma stained Plast Reconstr Surg 1984;74:694-8. for bcl-2, whereas all the cells in the BCC stained positive. 4. Duhra P, Paul Jc. Cryotherapy for multiple Of the immunohistochemical agents used, collagen IV trichoepithelioma. J Dermatol Surg Oncol 1988;14:1413--5. 5. DeVita VT, Hellman S, Rosenberg SA. Cancer: principles and and CD34 differentiated most clearly between BCC and practice of oncology. 4th ed. Philadelphia: JB Lippincott, trichoepithelioma. 1993. 6. Lever WF, Schaunburg-Lever G. Tumours of the epidermal appendages. In: Histopathology of the skin. 7th ed. Philadelphia: JB Lippincott, 1990:578--650. Discussion 7. Gaul LE. Heredity of multiple benign cystic epithelioma. Arch Dermatol Syph 1953;68:517-24. Trichoepithelioma, which is a benign lesion, can be 8. Zeligman 1. Solitary trichoepithelioma. Arch Dermatol removed by shave biopsy or close excision, and surgery 1960;82:35--40. 9. Takei Y, Fukushiro S, Ackerman AB. Criteria for histologic need not be as radical as for BCC? Conventional differentiation of desmoplastic trichoepithelioma (sclerosing management of BCC requires excision with a 3-4 mm epithelial hamartoma) from morphea-like basal cell margin and histological examination,1 or the use of carcinoma. Am J Dermatopathol 1985;7:207-21. 10. Brownstein MH, Shapiro L. Desmoplastic trichoepithelioma. microsurgery with frozen section control (Moh's Cancer 1977;40:2979-86. micrographic surgery),20 regardless of subsequent 11. Boring CC, Squires TS, Tong T. Cancer statistics. Cancer histology. This approach is based on retrospective 1992;42: 19-38. 12. Lober CW, Fenske NA. Basal cell, squamous cell and studies of outcome of excision of all BCCs and does not sebaceous gland carcinomas of the periorbital region. J Am take into account histological differentiation. Hence, Acad Dermatol 1991;25:685-90. conventional surgical management is based on surgery 13. Brooke JD, Fitzpatrick JE, Golitz LE. Papillary mesenchymal bodies: a histologic finding useful in differentiating required for the most aggressive, i.e. morpheaform, trichoepitheliomas from basal cell carcinomas. J Am Acad tumour. If BCC recurrence rates were looked at in terms Dermatol 1989;21:523-8. of histological type a smaller excision margin might be 14. Koboyasi T. Dermo-epidermal junction in basal cell adequate in selected cases. In the cases presented the carcinoma. Acta Derm Venereol 1970;50:40. 15. Hashimoto K, Yamahashi Y, Dabbous MK. Electron diagnosis of trichoepithelioma was suggested on microscope observations in vivo and in vitro: collagenolytic morphological criteria, but immunohistochemical activity of the basal cell epithelioma of the skin. Cancer Res features, which illustrate the architecture and integrity of 1972;32:2561. 16. Weber L, Krieg T, Muller PK, Kivsch E, Timpl R. the basement membrane in this tumour, provide Immunofluorescence localisation of type IV collagen and considerable help in confirming the diagnosis, laminin in human skin and its application in junction zone particularly when only a small biopsy is available. In pathology. Br J Dermatol 1982;106:267. 17. Kimura S, Yamasaki Y, Nishikawa S, Hotano H. A contrast, the disorganised nature of the basement comparative study of seborrhoeic keratoses and basal cell membrane in BCC is striking and highlights the epitheliomas by complement immunofluorescence and relatively undifferentiated nature of BCC compared with electron microscopy. Acta Derm VenereoI1980;60:203. 18. Kirchmann TT, Prieto VG, Smoller BR. CD34 staining pattern trichoepithelioma. distinguishes basal cell carcinoma from trichoepithelioma. Since trichoepithelioma is more common in young Arch Dermatol 1994;130:589-92. people, this diagnosis should be suspected in this 19. Smoller BR, van de Rijn M, Lebrun D, Warnke RA. bC/-2 subgroup prior to surgery and an incisional biopsy expression reliably distinguishes trichoepitheliomas from basal cell carcinomas. Br J Dermatol 1994;131:28-31. carried out. Excision can then be carried out with a small 20. Swanson NA. Moh's surgery: technique, indications, margin of healthy tissue, facilitating surgical repair. applications and the future. Arch Dermatol 1983;119:761-73.